This laboratory uses a proteomics approach to study the proteins of the normal human lens and in cataracts of various etiologies. Lens dissections are done to obtain age-defined populations of fiber cells from lenses of all ages. Methodologies have been developed to yield high resolution separation of these proteins using two-dimensional polyacrylamide gel electrophoresis. Identification of the proteins and the characterization of their post-translational modifications are done by matrix assisted laser desorption ionization time of flight and electrospray mass spectrometry. The study has demonstrated extensive post-translational modifications of the crystallins that occur early in life and the development of a unique protein pattern of the lens nuclear fiber cells. Pathways for the processing of alpha crystallins have been identified. In certain cataracts high concentrations of C-terminally cleaved forms of alpha crystallins are present. The protein patterns of numerous cataracts have been determined. These data are now being analyzed with respect to the cataract etiology. The proteins throughout the lens are being identified yielding a database of information on the normal human lens. Studies on the expression of alpha B-crystallin are being done to understand the effects of the C-terminal cleavage on structure and function and to understand the regulation of the expression of alpha B crystallin under stress.